Abstract
Importance Epidemiological studies suggest that lifestyle factors are associated with risk of dementia. However, few studies have examined the association of diet and waist to hip ratio (WHR) with hippocampus connectivity and cognitive health. Objective To ascertain how longitudinal changes in diet quality and WHR during midlife are associated with hippocampal connectivity and cognitive function in later life. Design, Setting, and Participants This cohort study analyzed data from participants in the Whitehall II Study at University College London (study inception: 1985) and Whitehall II Imaging Substudy at the University of Oxford (data collection: 2012-2016). Healthy participants from the Whitehall II Imaging Study with a mean age of 48 years at baseline to 70 years at magnetic resonance imaging (MRI) were included if they had information on diet from at least 1 wave, information on WHR from at least 2 waves, and good-quality MRI scans. Study analyses were completed from October 2019 to November 2024. Exposures Diet quality was measured in participants(mean age, 48 years at baseline to 60 years) using the Alternative Healthy Eating Index–2010 score, which was assessed 3 times across 11 years. WHR was measured 5 times over 21 years in participants aged 48 to 68 years. Main Outcomes and Measures White matter structural connectivity assessed using diffusion tensor imaging, hippocampal functional connectivity assessed using resting-state functional MRI, and cognitive performance measures. Brain imaging and cognitive tests were performed at a mean (SD) age of 70 (5) years. Results The final diet quality sample comprised 512 participants (403 males [78.7%]; mean [SD] age, 47.8 [5.2] years), and the final WHR sample included 664 participants (532 males [80.1%]; mean [SD] age, 47.7 [5.1] years). Better diet quality in midlife and from midlife to late life was associated with higher hippocampal functional connectivity to the occipital lobe and cerebellum (left hippocampus: 9176 mm 3 , P < .05; left hippocampus and to the right cerebellum: 136 mm 3 , P = .04) and better white matter integrity as measured by higher fractional anisotropy (FA; 19 432 mm 3 , P < .05) and lower diffusivity (mean diffusivity [MD]: 5560 mm 3 , P < .05; axial diffusivity [AD]: 2600 mm 3 , P < .045; AD in fornix: β [SE] = 0.26 [0.11], false discovery rate–corrected P = .02). Higher WHR in midlife was associated with higher MD and radial diffusivity (covering 26.4% [333 088 mm 3 , P < .001] and 23.1% [291 888 mm 3 , P < .05], respectively, of the total white matter tracts in the cingulum and superior and inferior longitudinal fasciculus) and lower FA in the corticospinal tract (covering 4.9% of the white matter skeleton), including the inferior longitudinal fasciculus and cingulum (61 272 mm 3 , P < .05). Associations between midlife WHR, working memory, and executive function were partially mediated by diffusivity (eg, digit span was mediated by global FA: β = –2.96 −03 ; 95% CI, –5.56 −03 to −1.01 −03 ; P < .001). Conclusions and Relevance This cohort study found that healthier diets and lower WHR throughout midlife were associated with better brain and cognitive health in older age. The findings suggest that interventions to improve diet and manage central obesity might be most effective between ages 48 and 70 years.